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丙烯酰胺使 C57BL/6J 小鼠肝脏和 HepG2 细胞中的生物钟和线粒体动态表达模式出现缺陷。

Acrylamide Defects the Expression Pattern of the Circadian Clock and Mitochondrial Dynamics in C57BL/6J Mice Liver and HepG2 Cells.

机构信息

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Xinong Road 2 , Yangling , Shaanxi 712100 , People's Republic of China.

出版信息

J Agric Food Chem. 2018 Oct 3;66(39):10252-10266. doi: 10.1021/acs.jafc.8b02473. Epub 2018 Sep 19.

Abstract

Circadian rhythm helps organisms adapt to their environment and control a variety of physiological and metabolic processes. Acrylamide is a toxic compound that can be produced during food processing. The aim of this research is to investigate whether the circadian clock is involved in the toxicity mechanisms of acrylamide in mice liver. Our results revealed that acrylamide markedly induced circadian gene oscillation disorder and blocked circadian-related protein in mice liver and HepG2 cells. Simultaneously, the balance of the daily oscillation of the antioxidant enzymes was impeded under acrylamide treatment. Furthermore, acrylamide treatment elevated the mitochondrial dynamic gene expressions and influenced the mitochondrial morphology at the night phase. Acrylamide blocked circadian protein expression via repressing the phosphorylation of AKT or inducing oxidative stress. Taken together, our work reveals acrylamide as a clock-repressing compound generated through the Maillard browning reaction in certain foods that may possess a toxic effect via circadian clock mechanisms.

摘要

昼夜节律有助于生物适应环境并控制各种生理和代谢过程。丙烯酰胺是一种在食品加工过程中产生的有毒化合物。本研究旨在探讨昼夜节律钟是否参与丙烯酰胺在小鼠肝脏中的毒性机制。我们的结果表明,丙烯酰胺显著诱导了昼夜节律基因振荡紊乱,并阻断了小鼠肝脏和 HepG2 细胞中的昼夜节律相关蛋白。同时,丙烯酰胺处理干扰了抗氧化酶的日常振荡平衡。此外,丙烯酰胺处理在夜间阶段升高了线粒体动力学基因的表达并影响了线粒体形态。丙烯酰胺通过抑制 AKT 的磷酸化或诱导氧化应激来阻断昼夜节律蛋白的表达。总之,我们的工作揭示了丙烯酰胺作为一种通过某些食物中的美拉德褐变反应产生的时钟抑制化合物,可能通过昼夜节律钟机制产生毒性作用。

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